Cholecystokinin facilitates glutamate release by increasing the number of readily releasable vesicles and releasing probability

Pan Yue Deng, Zhaoyang Xiao, Archana Jha, David Ramonet, Toshimitsu Matsui, Michael Leitges, Hee Sup Shin, James E. Porter, Jonathan D. Geiger, Saobo Lei

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Cholecystokinin (CCK), a neuropeptide originally discovered in the gastrointestinal tract, is abundantly distributed in the mammalian brains including the hippocampus. Whereas CCK has been shown to increase glutamate concentration in the perfusate of hippocampal slices and in purified rat hippocampal synaptosomes, the cellular and molecular mechanisms whereby CCK modulates glutamatergic function remain unexplored. Here, we examined the effects of CCK on glutamatergic transmission in the hippocampus using whole-cell recordings from hippocampal slices. Application of CCK increased AMPA receptor-mediated EPSCs at perforant path-dentate gyrus granule cell, CA3-CA3 and Schaffer collateral-CA1 synapses without effects at mossy fiber-CA3 synapses. CCK-induced increases in AMPA EPSCs were mediated by CCK-2 receptors and were not modulated developmentally and transcriptionally. CCK reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that CCK facilitates presynaptic glutamate release. CCK increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. CCK-mediated increases in glutamate release required the functions of phospholipase C, intracellular Ca2+ release and protein kinase Cγ. CCK released endogenously from hippocampal interneurons facilitated glutamatergic transmission. Our results provide a cellular and molecular mechanism to explain the roles of CCK in the brain.

Original languageEnglish (US)
Pages (from-to)5136-5148
Number of pages13
JournalJournal of Neuroscience
Volume30
Issue number15
DOIs
StatePublished - Apr 14 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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